Delivery of therapeutic drugs via the dermal route is a promising alternative to oral or parenteral delivery routes. Dermal drug delivery systems (3DS) offer unique advantages which include: controlled release over longer durations for steady absorption into the systemic circulation, reduced systemic toxicity, significant reduction in first pass effects and gastrointestinal irritation. The market potential of 3DS was valued at ~$13B in 2005, and is projected to reach ~$40B by 2018, suggesting significant investment by pharma companies in dermal drug research. In response to this trend, a robust simulation tool that can help predict the safety and effectiveness of new pharmaceuticals, bioequivalence of generics, intended for transdermal delivery will be indispensable to pharma industry to accelerate development for regulatory approval towards market launch. Towards this goal, we propose to develop a toolkit for Computational Pharmacotherapy of Dermally Administered Compounds, abbreviated CPDAC. The multiscale toolkit will integrate a holistic model of dermal absorption and transport, and whole body physiology based pharmacokinetics (PBPK) for predicting pharmacokinetics (PK) and pharmacodynamics (PD) of drugs in a unified framework. The tool will be designed in a modular/parametric form to accommodate subject-specific physiology, user-defined fidelities of specific skin layers (0D-3D), embedded microvasculature, and tool compound formulations and different dermal delivery routes. In Phase I, we will predict the PK of multiple drugs for Gen-1 delivery routes (transdermal patch, gel and spray) and validate with literature data. In Phase II, we plan to extend the scope of the toolkit to include Gen-2 field assisted transdermal systems and Gen-3 intradermal delivery. We will also develop and demonstrate intelligent algorithms to correlate the PK/PD outcomes to predict the human safety and effectiveness of novel compounds tested in vitro. 1